Comparison of the antipyretic actions of indomethacin and L-745,337, a selective cyclooxygenase-2 inhibitor, in endotoxin-treated prepubertal pigs.
1. The growing pig provides a useful, nonrodent model for studying mechanisms involved in the febrile response. 2. Indomethacin (IND) has previously been shown to prevent lipopolysaccharide (LPS) fever in prepubertal pigs. 3. This study compared the abilities of IND and L-745,337, a novel cyclooxygenase-2 (cox-2) inhibitor, to counteract the effects a low dose of LPS (20 micrograms/pig IV) on deep body temperature. Effects of IND and L-745,337 on core temperature and plasma cortisol concentrations were also examined in nonfebrile animals. 4. L-745,337 (0.3 mg/kg IV) did not alter the response to LPS, whereas both IND and L-745,337 (1.7 mg/kg) reduced the febrile effects of LPS given 60 min earlier. 5. Neither IND, nor L-745,337 (1.7 mg/kg IV) affected core temperature in nonfebrile animals whereas IND, but not L-745,337, stimulated cortisol release. 6. The results suggest that prostaglandin modulates the febrile effects of LPS in swine and that inhibition of inducible cyclooxygenase (Cox-2) suppresses fever without producing the stressful side-effects that accompany constitutive cyclooxygenase (Cox-1) inhibition, as exemplified by IND (a mixed Cox-1/Cox-2 antagonist).
Parrott
R F
RF
MAFF Welfare and Behaviour Laboratory, Department of Neurobiology, Babraham Institute, Cambridge, England.
Vellucci
S V
SV
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D005334:Fever / Q000188:drug therapy / Q000201:enzymology; D006854:Hydrocortisone / Q000097:blood; D007189:Indans / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology*; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D013552:Swine
D018712:Analgesics, Non-Narcotic; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007189:Indans; D007527:Isoenzymes; C093700:L 745337; D008070:Lipopolysaccharides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D006854:Hydrocortisone; D007213:Indomethacin